Article
Biochemistry & Molecular Biology
Mohini S. Ghatge, Mohammed Al Mughram, Abdelsattar M. Omar, Martin K. Safo
Summary: This article discusses the biochemical features of inborn errors related to deficiency in salvage enzymes for PLP, leading to NEE and other pathologies. Perspectives on vitamin B6 treatment for these disorders are presented, along with attempts to develop a zebrafish model to study the NEE syndrome in vivo.
Review
Nutrition & Dietetics
Felix Hadtstein, Misha Vrolijk
Summary: Studies have shown that excessive intake of pyridoxine (PN) can lead to sensory peripheral neuropathy, possibly through genetic mutations of the PDXK gene causing hereditary neuropathy. This mechanism may be related to the neurotransmitter gamma-aminobutyric acid (GABA).
ADVANCES IN NUTRITION
(2021)
Article
Chemistry, Physical
O. N. Krutova, A. Lytkin, V. V. Chernikov, A. V. Volkov, Yu Mokhova, P. D. Krutov
Summary: The study measured the enthalpies of dissolution of crystalline pyridoxine and pyridoxal-5'-phosphate in water and KOH aqueous solutions using a direct calorimetric method. The standard enthalpies of combustion and formation were calculated based on group systematics and the effect of primary environment for atoms were taken into account. Additionally, the standard enthalpies of formation and dissociation products in aqueous solutions were also calculated.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Microbiology
Tomokazu Ito, Honoka Ogawa, Hisashi Hemmi, Diana M. Downs, Tohru Yoshimura
Summary: PLPBP plays a crucial role in vitamin B-6 homeostasis. This study reveals the mechanism of intracellular accumulation of PNP due to the loss of PLPBP and suggests that disruption of PLPBP perturbs PMP homeostasis.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Genetics & Heredity
Remi Denise, Jill Babor, John A. Gerlt, Valerie de Crecy-Lagard
Summary: Using a comparative genomic approach, the synthesis and salvage pathways of PLP were predicted in 5840 bacterial and archaeal species. It was found that many organisms lack key genes involved in PLP synthesis pathways, and further research is needed to identify potential transporters. This work provides a starting point for modeling the exchanges of B6 vitamers, predicting sensitivity to drugs targeting PLP synthesis enzymes, and addressing gaps in knowledge.
MICROBIAL GENOMICS
(2023)
Review
Chemistry, Applied
A. J. M. Santos, S. Khemiri, S. Simo, C. Prista, I. Sousa, A. Raymundo
Summary: Vitamins are essential organic compounds that are necessary for good health but cannot be synthesized by the human body. Vitamins B6 and B12 are hydrophilic vitamins that play vital roles in cellular operation, growth, and development. This review focuses on the important aspects of vitamins B6 and B12, including their roles, consequences of deficiency, food sources, and chromatographic techniques developed in the last two decades for their determination.
Article
Multidisciplinary Sciences
Elesha R. Hoffarth, Kersti Caddell Haatveit, Eugene Kuatsjah, Gregory A. MacNeil, Simran Saroya, Charles J. Walsby, Lindsay D. Eltis, K. N. Houk, Marc Garcia-Borras, Katherine S. Ryan
Summary: Recent study uncovers a mechanism by which the organic cofactor PLP activates molecular oxygen for oxidation reactions, particularly in the desaturation or hydroxylation of arginine. The proposed mechanism suggests the precise positioning of a water molecule in the active site plays a crucial role in controlling the final reaction outcome. This mechanism provides a unified framework to understand the activation of oxygen by PLP-dependent enzymes and elucidates a shared mechanistic pathway and intertwined evolutionary history for arginine desaturases and hydroxylases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Clinical Neurology
Greta Amore, Ambra Butera, Giulia Spoto, Giulia Valentini, Maria Concetta Saia, Vincenzo Salpietro, Francesco Cali, Gabriella Di Rosa, Antonio Gennaro Nicotera
Summary: KCNQ2 gene mutations have been associated with neonatal epilepsy. This study reports two cases of KCNQ2-related neonatal epilepsy successfully treated with vitamin B6, suggesting that it can be an effective treatment option. Further research is needed to establish clinical guidelines and treatment protocols.
FRONTIERS IN NEUROLOGY
(2022)
Article
Pharmacology & Pharmacy
Pramod Reddy
Summary: Vitamin B6 is essential for physiological processes in the human body, and PLP-based supplements are preferred. The currently recommended dietary intake of B6 may not ensure adequate status, while high doses of B6 may lead to neurotoxicity.
AMERICAN JOURNAL OF THERAPEUTICS
(2022)
Review
Endocrinology & Metabolism
Barbara Plecko
Summary: In the past two decades, the field of vitamin B-6-dependent epilepsies has made significant progress in identifying gene defects and biomarkers related to reduced availability of pyridoxal 5-phosphate. These defects lead to severe seizures in newborns and require urgent medical attention. Standardized trials with vitamin B-6 should be implemented to detect and treat these inborn errors of metabolism. The Komrower lecture of 2022 highlighted the importance of collaboration between clinician scientists and basic researchers in understanding the pathomechanisms of vitamin metabolism and improving patient care.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Biotechnology & Applied Microbiology
Huong N. Vu, Diana M. Downs
Summary: This study reveals a mechanism in Salmonella enterica for salvaging phosphorylated B-6 vitamers utilizing the periplasmic phosphatase PhoN. The findings suggest a unique strategy for energy conservation in species across domains of life and shed light on the general role of promiscuous phosphatases and kinases in organismal fitness.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Julia Rossmann, Stine Christ, Sylvia Richter, Sven Friedrich Garbade, Georg Friedrich Hoffmann, Thomas Opladen, Juergen Guenther Okun
Summary: Vitamin B-6 and its metabolites play a crucial role in brain metabolism. Accurate and reliable detection of vitamin B-6 metabolites is important for clinical diagnosis. This study presents a new method for analyzing and quantifying vitamin B-6 vitamers in human CSF samples, which is significant for routine diagnostic laboratories.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anna Barile, Philippa Mills, Martino L. di Salvo, Claudio Graziani, Victoria Bunik, Peter Clayton, Roberto Contestabile, Angela Tramonti
Summary: The study characterized the catalytic, allosteric, and structural properties of PNPO variants, including D33V, R161C, P213S, and E50K. D33V and E50K variants had mildly altered catalytic properties, while P213S had lower thermal stability and reduced cofactor binding capability. The R161C variant significantly decreased substrate affinity and abolished allosteric feedback inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Lei Xu, Yu-Jing Fang, Meng-Meng Che, Alinuer Abulimiti, Chu-Yi Huang, Cai-Xia Zhang
Summary: This study investigated the relationship between vitamin B-6 and colorectal cancer risk using biomarkers PLP, PL, and PAr. The results showed that serum PLP and the sum of PLP and PL were inversely associated with colorectal cancer risk, while PAr was positively associated with colorectal cancer risk. The study suggested that vitamin B-6 may have a protective role in reducing colorectal cancer risk in the Chinese population, and that inflammation and oxidative stress may play a potential role in colorectal carcinogenesis.
Article
Chemistry, Medicinal
Rajashree Pawar, Preeti Chaudhran, Dheeraj Pandey, Abha Sharma
Summary: Pyridoxine and its derivatives, pyridoxamine, and pyridoxal, have been studied for over 70 years for their roles in regulating cellular biology and metabolism. Recent investigations have revealed the antioxidant and anti-inflammatory properties of pyridoxine and its vitamers. However, in the past two decades, researchers have observed interesting chemical modifications of pyridoxine. The pathophysiological aspects of pyridoxine and its derivatives in various cellular systems have been discovered, linking them to diseases such as cancer, diabetes, hypertension, tuberculosis, epilepsy, and neurodegenerative diseases. This review aims to highlight the importance of pyridoxine and its derivatives, obtained through chemical modifications, in different disease areas and identify future research directions.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Roberto Contestabile, Martino Luigi di Salvo, Victoria Bunik, Angela Tramonti, Fiammetta Verni
Article
Biochemistry & Molecular Biology
Elisa Mascolo, Francesco Liguori, Lorenzo Stufera Mecarelli, Noemi Amoroso, Chiara Merigliano, Susanna Amadio, Cinzia Volonte, Roberto Contestabile, Angela Tramonti, Fiammetta Verni
Summary: In this study, silencing of Hex-A and Hex-C in Drosophila resulted in a MODY-2-like hyperglycemia phenotype. Hex-A is crucial for insulin secretion and required for Hex-C expression. Reduced levels of either Hex-A or Hex-C led to chromosome aberrations and increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). Treating GCK-depleted larvae with the antioxidant vitamin B6 rescued chromosome aberrations, while treatment with a B6 inhibitor enhanced genomic instability, suggesting a link between MODY-2 and genome integrity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anna Barile, Theo Battista, Annarita Fiorillo, Martino Luigi di Salvo, Francesco Malatesta, Angela Tramonti, Andrea Ilari, Roberto Contestabile
Summary: PLP, the active form of vitamin B6, is crucial in metabolism as an enzyme cofactor. In Escherichia coli, PNPO catalyzes PLP formation and is inhibited by the same molecule through allosteric regulation. Crystallographic studies identified the allosteric site of PLP on PNPO, and mutagenesis of the arginine cage can modulate the enzyme's allosteric properties.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Angela Tramonti, Roberto Contestabile, Rita Florio, Caterina Nardella, Anna Barile, Martino L. Di Salvo
Summary: In this study, human cysteine sulfinic acid decarboxylase was recombinantly expressed, purified, and its enzymatic activity measured using a simple spectroscopic direct method based on circular dichroism. The enzyme was found to catalyze decarboxylation of additional substrates besides its natural ones, albeit with lower efficiency, providing new insights into its catalytic mechanism.
Article
Oncology
Angela Tramonti, Elisabet Cuyas, Jose Encinar, Matthias Pietzke, Alessio Paone, Sara Verdura, Aina Arbusa, Begona Martin-Castillo, Giorgio Giardina, Jorge Joven, Alexei Vazquez, Roberto Contestabile, Francesca Cutruzzola, Javier Menendez
Summary: Metformin functions as a novel non-catalytic inhibitor of SHMT2 by disrupting the PLP-dependent oligomerization process, which could lead to the development of novel SHMT2 inhibitors.
Article
Chemistry, Medicinal
Vasily A. Aleshin, Anastasia V. Graf, Artem V. Artiukhov, Alexandra I. Boyko, Alexander L. Ksenofontov, Maria V. Maslova, Isabel Nogues, Martino L. di Salvo, Victoria I. Bunik
Summary: The study reveals that the disturbed metabolism of vitamins B1 or B6 may cause seizures, especially with stronger PTZ sensitivity in female rats. Female rats show delayed seizure with administration of vitamins B1 and B6, indicating potential therapeutic effects. Sex differences in behavior and brain biochemistry after a seizure suggest that epilepsy has sex-specific impacts on physiological and biochemical processes in the brain.
Article
Biochemistry & Molecular Biology
Anna Barile, Philippa Mills, Martino L. di Salvo, Claudio Graziani, Victoria Bunik, Peter Clayton, Roberto Contestabile, Angela Tramonti
Summary: The study characterized the catalytic, allosteric, and structural properties of PNPO variants, including D33V, R161C, P213S, and E50K. D33V and E50K variants had mildly altered catalytic properties, while P213S had lower thermal stability and reduced cofactor binding capability. The R161C variant significantly decreased substrate affinity and abolished allosteric feedback inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dalila Boi, Fani Souvalidou, Davide Capelli, Federica Polverino, Grazia Marini, Roberta Montanari, Giorgio Pochetti, Angela Tramonti, Roberto Contestabile, Daniela Trisciuoglio, Patrizia Carpinelli, Camilla Ascanelli, Catherine Lindon, Alessandro De Leo, Michele Saviano, Roberto Di Santo, Roberta Costi, Giulia Guarguaglini, Alessandro Paiardini
Summary: The study identified compounds that disrupt the interaction between AURKA and N-Myc, inhibiting growth of neuroblastoma cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Elisa Mascolo, Francesco Liguori, Chiara Merigliano, Ludovica Schiano, Eleonora Gnocchini, Eleonora Pilesi, Cinzia Volonte, Martino L. Di Salvo, Roberto Contestabile, Angela Tramonti, Fiammetta Verni
Summary: The impaired activity of PI3K is closely linked to genomic instability, and reduced PI3K activity leads to both hyperglycemia and chromosome aberrations. Vitamin B6 supplementation can rescue these defects.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Plant Sciences
Isabel Nogues, Bartosz Sekula, Sebastiana Angelaccio, Marta Grzechowiak, Angela Tramonti, Roberto Contestabile, Milosz Ruszkowski
Summary: Serine hydroxymethyltransferase (SHM) is an important enzyme involved in one-carbon metabolism in plants. Plant genomes encode multiple isoforms of SHM that have different tissue-specific expression patterns and catalytic properties. Some isoforms were not able to be rescued, suggesting distinct physiological functions. Comparative analysis of their three-dimensional structures revealed differences in regions surrounding the active site cavity.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Article
Entomology
Valentina Lucchesi, Lorenzo Grimaldi, Valentina Mastrantonio, Daniele Porretta, Letizia Di Bella, Tania Ruspandini, Martino Luigi Di Salvo, John Vontas, Romeo Bellini, Agata Negri, Sara Epis, Silvia Caccia, Claudio Bandi, Sandra Urbanelli
Summary: Insect pests are a global problem and controlling them is crucial for human well-being. Insecticides, specifically chitin-synthesis inhibitors (CSIs), are commonly used to control these pests, but resistance is developing in many species. This study focused on the molecular and phenotypic characteristics of the homozygous I1043M strain in Culex pipiens mosquitoes, which showed a high level of resistance to the CSI diflubenzuron. The researchers found that resistant mosquitoes had cuticle modifications and over-expression of the chs1 gene, which likely contribute to resistance. These findings are valuable for understanding CSI resistance in mosquitoes and other arthropod pests.
Article
Cell Biology
Eleonora Pilesi, Chiara Angioli, Claudio Graziani, Alessia Parroni, Roberto Contestabile, Angela Tramonti, Fiammetta Verni
Summary: Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, plays a crucial role in the 1C pathway for DNA metabolism. Deficiency of PLP can lead to chromosome damage by reducing the activity of serine hydroxymethyltransferase (SHMT) and impairing thymidylate synthesis. Our study in Drosophila suggests a gene-nutrient interaction between decreased SHMT activity and PLP deficiency, impacting genome stability.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)